title: Hedgehog signaling regulates size of the dorsal aortae and density of the plexus during avian vascular development.
abstract: Signaling by the hedgehog (Hh) family of secreted growth factors is essential for development of embryonic blood vessels. Embryos lacking Hh function have abundant endothelial cells but fail to assemble vascular cords or lumenized endothelial tubes. However, the role of Hh signaling during later aspects of vascular patterning and morphogenesis is largely unexplored. We have used small molecule inhibitors and agonists to alter activity of the Hh signaling pathway in the chick embryo. When cyclopamine is added after cord formation, aortal cells form tubes, but these are small and disorganized and the density of the adjacent vascular plexus is reduced. Activation of the Hh pathway with SAG leads to formation of enlarged aortae and increased density of the plexus. The number of endothelial cell filopodia is found to correlate with Hh signaling levels. These studies show that Hh signaling levels must be tightly regulated for normal vascular patterning to be achieved.
authors.affiliation: Department of Cellular and Molecular Medicine, Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Moran
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Salanga
authors.forename: Paul A
authors.initials: PA
authors.lastname: Krieg
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D001717:Birds / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D002452:Cell Count; D002642:Chick Embryo; D003514:Cyclohexylamines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D053823:Hedgehog Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013723:Teratogens / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D003514:Cyclohexylamines; D053823:Hedgehog Proteins; C468918:SAG compound; D013723:Teratogens; D013876:Thiophenes; D014704:Veratrum Alkaloids; C000541:cyclopamine